N-dCas9(4)::FRB and FKBP::C-dCas9(4)::VPR form the two halves of a rapamycin-regulated split driver system that when combined can reconstitute a functional transcriptional activator ('driver') in which 'dCas9' (a catalytically inactive form of the Cas9 endonuclease from Streptococcus pyogenes) is fused to 'VPR', a tripartite fusion of three transcription activation domains: VP64, p65 and Rta. N-dCas9(4)::FRB consists of an N-terminal fragment of Cas9 (residues 2-535) that has been mutated to carry a D10A amino acid substitution in the RuvC domain, and is tagged at the N-terminal end with a nuclear export signal (NES) and at the C-terminal end with Tag:FRB. FKBP::C-dCas9(4)::VPR consists of a C-terminal fragment of Cas9 (residues 536-1368) that has been mutated to carry a N863A amino acid substitution in the HNH domain, and is tagged at the N-terminal end with both a nuclear localization signal (NLS) and Tag:FKBP and at the C-terminal end with a second NLS followed by the VPR transcription activation domain module. In the absence of rapamycin, the two split portions are separated into the nuclear and cytoplasmic compartments (due to the presence of the NES in N-dCas9(4)::FRB and the NLS sequences in FKBP::C-dCas9(4)::VPR). In the presence of rapamycin, heterodimerization of Tag:FRB and Tag:FKBP promotes the association of N-dCas9(4)::FRB and (newly synthesized) FKBP::C-dCas9(4)::VPR proteins, reconstituting a functional driver that is translocated to the nucleus due to the presence of the NLS sequences in FKBP::C-dCas9(4)::VPR. The reconstituted driver can be used to overexpress a target gene of interest from its endogenous genomic locus, by combining it with a single guide RNA (sgRNA) that targets sequences upstream of the gene of interest's transcription start site (PMID:25643054, FBrf0245398).